This pilot intervention study is designed to determine whether aspirin (ASA) can normalize the colorectal mucosa] hyperproliferation found in patients with adenomatous polyps. ASA is a non-steroidal anti-inflammatory drug (NSAID) which acts via depletion of prostaglandins (PG). High concentrations of PGs have been found in human cancer tissues and NSAIDs have been shown to inhibit cell cycle progression and cell growth in vitro, as well as inhibit tumor growth in animal models in vivo. Recent epidemiologic data suggest that ASA use may be associated with a decrease in colorectal cancer risk or mortality. Several small clinical trials have suggested that NSAIDs may reduce the number of adenomatous polyps in patients with multiple adenomas. We thus seek to determine whether ASA may decrease rectal mucosal proliferation and whether there is any association with decreased PGs. ASA was chosen because of its low cost, relative safety, large clinical experience, and recent studies showing its efficacy in primary and secondary prevention of myocardial and cerebrovascular events. The study will enter 160 post-polypectomy (adenomas) patients (of whom 120 will complete study), stratified by age (less than 45, 45-65, and greater than 65 years) into a double-blind, randomized, placebo-controlled cross-over study of 325 mg/day and 81 mg/day of ASA, with each treatment cycle lasting 3 months. At the beginning and end of each 3 month treatment cycle, sigmoidoscopy and biopsy will be done and rectal mucosa will be assayed for bromodeoxyuridine, proliferating cell nuclear antigen (PCNA), ornithine decarboxylase, polyamines and PGs. Patients will also be monitored for potential toxicity via questionnaire, blood chemistries and blood counts, and gastroduodenoscopy and fecal occult blood. Adherence will be monitored, including the use of serum ASA levels, and an adherence reinforcement program will be in place. The results will allow us to determine whether 325 mg/day or 81 mg/day of ASA will suppress mucosal proliferation as measured by the four proliferation markers, whether there is any association with age and with depletion of PGs, and whether there are any clinically important toxicities. The results may thus allow us to determine whether ASA should be further tested, to choose an optimal dose of ASA for full-scale clinical trials, and to determine whether ASA dose needs to be adjusted for age.